TLR9 and CYP3A5 polymorphisms influence the risk of BK polyomavirus reactivation in Chinese kidney transplant recipients.

BACKGROUND: Genetic determinants of BK polyomavirus (BKV) reactivation after kidney transplantation are poorly explored. We assessed the associations between polymorphisms in TLR3, TLR9, IL6, and CYP3A5 genes and BKV reactivation risk among Chinese kidney transplant recipients, with BKV DNAuria as the primary endpoint. METHODS: A total of 133 kidney transplant recipients were prospectively enrolled and followed for 12 months. BKV DNAuria and DNAemia were monitored by real-time PCR monthly for the first 6 months post-transplantation and then quarterly thereafter. Genotyping of TLR3 rs3775290, rs3775291, and rs3775296, TLR9 rs5743836 and rs352140, IL6 rs1800796, and CYP3A5 rs776746 was performed using improved multiplex ligase detection reaction or commercial kits. RESULTS: The 12-month cumulative incidence of BKV DNAuria was 49.6% (95% CI: 41.0-58.2), with 6.0% (8/133) of patients developing BKV DNAemia. TLR9 rs352140 TT carriers showed lower BKV DNAuria-free survival than CC/CT carriers (18.2% vs. 53.3%, log-rank P = 0.005), corresponding to a higher DNAuria incidence (81.8% vs. 40.4% in CC carriers and 51.4% in CT carriers). However, this TT subgroup finding (n = 11) has limited power, warranting cautious interpretation. CYP3A5 rs776746 AA/AG carriers had higher DNAuria rates (68.8% and 59.3%) than GG carriers (36.5%, P = 0.013), and GG carriers exhibited superior DNAuria-free survival (63.5% vs. 38.6%, P = 0.002). An additive effect of risk genotypes was also observed, with DNAuria-free survival decreasing progressively as the number of risk genotypes increased (log-rank P = 0.001). CONCLUSIONS: TLR9 rs352140 represents an exploratory risk signal for BKV reactivation, while CYP3A5 rs776746 is significantly associated with elevated reactivation risk in Chinese kidney transplant recipients. The cumulative burden of these two risk genotypes further increases susceptibility. Genetic profiling of these loci may aid in risk stratification, pending larger cohort validation for the TLR9-related association.